Role of acetoin on the regulation of intermediate metabolism of Ehrlich ascites tumor mitochondria: its contribution to membrane cholesterol enrichment modifying passive proton permeability.
Acetoin, an unusual metabolite of highly glycolytic mammalian tumor cells, is synthesized from decarboxylated pyruvate and active acetaldehyde in mitochondria. It plays important roles in the regulation and detoxification of pyruvate metabolism through pyruvate dehydrogenase. We show in this report the inhibitory effect of acetoin on succinate oxidation by Ehrlich tumor cell mitochondria, and thus its regulatory role on intermediate metabolism. Acetoin utilization by Ehrlich mitochondria may lead to small quantities of citrate formation which increase the already increased cholesterol synthesis of cancer cells. Membranes, in particular the inner mitochondrial membrane, flooded with cholesterol, show a proton passive permeability twice as low as that of control mitochondrial membranes, a feature that may be related to drastic changes in membrane potential-dependent metabolism of cancer cells.
Baggetto
L G
LG
LBTMSI-CNRS, Université Claude Bernard Lyon 1, Villeurbanne, France.
Testa-Parussini
R
R
D000093:Acetoin / Q000378:metabolism*; D000818:Animals; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D002951:Citrates / Q000378:metabolism; D006019:Glycolysis; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008293:Malates / Q000378:metabolism; D008297:Male; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000378:metabolism; D008954:Models, Biological; D010101:Oxygen Consumption; D010539:Permeability; D051381:Rats; D011919:Rats, Inbred Strains
D002951:Citrates; D008293:Malates; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D002784:Cholesterol; D000093:Acetoin